rs1057079
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_004958.4(MTOR):c.4731G>A(p.Ala1577=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,613,390 control chromosomes in the GnomAD database, including 413,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.56 ( 29032 hom., cov: 31)
Exomes 𝑓: 0.72 ( 384315 hom. )
Consequence
MTOR
NM_004958.4 synonymous
NM_004958.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.869
Genes affected
MTOR (HGNC:3942): (mechanistic target of rapamycin kinase) The protein encoded by this gene belongs to a family of phosphatidylinositol kinase-related kinases. These kinases mediate cellular responses to stresses such as DNA damage and nutrient deprivation. This kinase is a component of two distinct complexes, mTORC1, which controls protein synthesis, cell growth and proliferation, and mTORC2, which is a regulator of the actin cytoskeleton, and promotes cell survival and cell cycle progression. This protein acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. Inhibitors of mTOR are used in organ transplants as immunosuppressants, and are being evaluated for their therapeutic potential in SARS-CoV-2 infections. Mutations in this gene are associated with Smith-Kingsmore syndrome and somatic focal cortical dysplasia type II. The ANGPTL7 gene is located in an intron of this gene. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
?
Variant 1-11145001-C-T is Benign according to our data. Variant chr1-11145001-C-T is described in ClinVar as [Benign]. Clinvar id is 516654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-11145001-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.869 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTOR | NM_004958.4 | c.4731G>A | p.Ala1577= | synonymous_variant | 33/58 | ENST00000361445.9 | |
MTOR-AS1 | NR_046600.1 | n.310+115C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTOR | ENST00000361445.9 | c.4731G>A | p.Ala1577= | synonymous_variant | 33/58 | 1 | NM_004958.4 | P1 | |
MTOR-AS1 | ENST00000445982.5 | n.310+115C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.564 AC: 85698AN: 151880Hom.: 29024 Cov.: 31
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GnomAD3 exomes AF: 0.686 AC: 172411AN: 251352Hom.: 62071 AF XY: 0.692 AC XY: 93952AN XY: 135848
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GnomAD4 exome AF: 0.718 AC: 1049597AN: 1461392Hom.: 384315 Cov.: 51 AF XY: 0.717 AC XY: 521497AN XY: 727030
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GnomAD4 genome ? AF: 0.564 AC: 85707AN: 151998Hom.: 29032 Cov.: 31 AF XY: 0.567 AC XY: 42106AN XY: 74304
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 29, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at